title: Immature renal structures associated with a novel UMOD sequence variant.
abstract: Mutations of the UMOD gene, encoding uromodulin, have been associated with medullary cystic kidney disease 2, familial juvenile hyperuricemic nephropathy, and glomerulocystic kidney disease. We report on a 13-year-old boy presenting with chronic reduced kidney function, hyperuricemia, and impairment in urine-concentrating ability. His father was affected by an undefined nephropathy that required transplantation. The boy's renal ultrasonography showed reduced bilateral kidney volumes and cortical hyperechogenicity, with 2 tiny cysts in the left kidney. Renal biopsy showed up to 60% of glomeruli featuring an enlargement of Bowman space (glomerular cysts), with mild interstitial fibrosis (alpha-smooth muscle actin [alphaSMA] positive), inflammatory infiltrate, and focal tubular atrophy at the cortical level. At the corticomedullary junction, immature tubules (some dilated) with cytokeratin- and paired box gene 2 (PAX2)-positive immunostaining were seen, surrounded by vimentin-positive mesenchymal tissue. Unlike previously reported cases, no uromodulin-positive globular aggregates within the cytoplasm of tubular cells were observed. Uromodulin urinary excretion was absent. Genetic analysis showed a novel heterozygous sequence change in the UMOD gene (NM_003361.2:c.149G-->C; p.Cys50Ser) involving the first epidermal growth factor-like domain of the protein in both the boy and his father. This novel UMOD sequence variant, which is associated with an immunohistochemical pattern different from previous reports and a histological picture characterized by immature renal structures, suggests a possible role for UMOD in renal development.
authors.affiliation: Pediatric Nephrology, Dialysis, and Transplantation Unit, Department of Pediatrics, University of Padua, Padova, Italy. elisabene@libero.it
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Manuela Della
authors.initials: MD
authors.lastname: Vella
authors.forename: Luca
authors.initials: L
authors.lastname: Rampoldi
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Lina
authors.initials: L
authors.lastname: Artifoni
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D006801:Humans; D007672:Kidney Cortex / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D009088:Mucoproteins / Q000235:genetics*; D020125:Mutation, Missense; D058949:Uromodulin
chemical_list: D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin